In 1976, he graduated from The Fine Arts Education School of the Education Department of Tokyo Liberal Arts University ("Tokyo Gakugei Daigaku"). The following year, he entered Tatsunoko Productions and worked on his first anime as animation director on Ippatsu Kanta-kun. In 1980, he moved to Studio Pierrot under the supervision of his mentor, Hisayuki Toriumi. During production of the Nils no fushigi na tabi ("Wonderful Adventures of Nils") and Kagaku Ninja-Tai Gatchaman II TV series, Oshii first met longtime collaborators, writer Itou Kazunori and painter and character designer Amano Yoshitaka.

Between production of the Patlabor movies/series, Oshii directed three live action films. The first was The Red Spectacles (1987) which led into his later work Stray Dogs: Kerberos Panzer Cops (1991). The third was Talking Head (1992), a surreal look at Oshii's view on film executed through a plot about an anime production where the director is missing and has to be replaced by a new one.

In 1995, Mamoru Oshii released his landmark animated cyberpunk film, Ghost in the Shell, in Japan, the United States, and Europe simultaneously. It hit the top of the US Billboard video charts in 1996.

After a 5-year hiatus from directing to work on other projects, Oshii returned to directing with the long-awaited Japanese-Polish live action film Avalon shown at the Cannes Film Festival in 2001. His latest animated film Innocence: Ghost in the Shell was selected to compete at 2004 Cannes Film Festival for the coveted Palme d'Or prize, the first animated film in this top category and only the sixth animated film shown at Cannes. The festival described Innocence as a film in which "the political tone has given way to a philosophical one, a hymn to life. Furthermore, the technical rendering is much more formal, mixing 2D, 3D and computer graphics."